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Catalytic Site Atlas

CSA LITERATURE entry for 1idt

E.C. name6,7-dihydropteridine reductase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 1.5.1.34
CSA Homologues of 1idt
CSA Entries With UniProtID P38489
CSA Entries With EC Number 1.5.1.34
PDBe Entry 1idt
PDBSum Entry 1idt
MACiE Entry M0211

Literature Report

IntroductionEscherichia coli nitroreductase (NTR) reduces a wide range of nitroaromatic containing compounds to hydroxylamines and quinones to quinols. Some nitro containing antibiotics depend on activation by bacterial NTR . The native enzyme shows that the principal structural changes occur in the FMN cofactor and indicate that the enzyme itself is a relatively rigid structure that primarily provides a rigid structural framework on which hydride transfer occurs.
MechansimThe reaction proceeds by reduction of the nitro group of the prodrug substrate, forming a hydroxylamine product in a ping-pong Bi-Bi reaction pathway. Prior to the substrate binding, FMN accepts a hydride from NAD(P)H onto N1 or N5. NAD(P)H then leaves as NAD(P)+. The resultant negative charge is transferred through the delocalised system onto O3 where electrostatic interactions with K14 and K74 stabilise it. The nitro group to be attacked stacks above FMN which then transfers the hydride. At the same time the nitro group accepts a proton from water . The resultant -N(OH)2 group spontaneously eliminates water. A second hydride is passed to FMN by NAD(P)H, the charge again moves to O3 where it is best stabilised followed by transfer of the hydride to the nitroso group which simultaneously accepts a proton from water onto the oxygen, leading to the product.
Reaction

Catalytic Sites for 1idt

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
LysA7474macie:sideChainElectrostatic stabilisation of charge build up on the FMN at O3 during hydride transfer.
LysA1414macie:sideChainElectrostatic stabilisation of charge build up on the FMN at N1 and O3 during hydride transfer.

Annotated By Reference To The Literature - Site 4 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
LysB7474macie:sideChainElectrostatic stabilisation of charge build up on the FMN at O3 during hydride transfer.
LysB1414macie:sideChainElectrostatic stabilisation of charge build up on the FMN at N1 and O3 during hydride transfer.

Literature References

Notes:Water is suggested here as the proton donor as there is no evidence that a residue acts as a base.
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